Exchangeable apolipoproteins play a critical role in plasma lipoprotein metabolism, first as structural components of
lipoproteins, but also as activators of lipid metabolic enzymes at the surface of the lipoproteins and as ligands for cell surface receptors.
These functions are extremely important in the transport and the metabolism of lipids and cholesterol into the blood stream. While
the high-resolution structure of some of these proteins is known in the lipid-free state, much less is known about their
lipid-bound conformations. Yet, these lipid-bound conformations are the most important ones because an essential step in the activation of
these exchangeable apolipoproteins is their association with lipoprotein particles. Apolipoprotein E (apoE) is one of the most
important exchangeable apolipoproteins. In the lipid-bound state, apoE is a ligand for most of the receptors of the low-density
lipoprotein (LDL) receptor family. This makes apoE an extremely important anti-atherogenic component of the lipoprotein metabolism. We
study apoE lipid-bound conformation(s) and its interaction with its receptor, using different biochemical and structural
approaches (infrared spectroscopy, circular dichroism, NMR, and also bioinformatics). ApoE plays an extremely important role also in the
central nervous system and seems to be involved in neuronal plasticity, repair and development. One isoform of apoE, apoE4 has been
identified as one of the major risk factor in the development of Alzheimer's disease. ApoE is known to interact with the amyloid
beta peptide, considered as one of the major culprits in Alzheimer's disease. One of our goals is to study, using different
functional and structural approaches, the interaction of apoE with amyloid beta and to understand how apoE isoforms differentially
modulates the amyloid beta conformation.